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AZD-9291 (Synonyms: osimertinib)

Catalog No.GC16308

AZD-9291 (AZD9291) est un inhibiteur covalent, actif par voie orale, irréversible et sélectif pour les mutants de l'EGFR avec une IC50 apparente de 12 nM contre L858R et 1 nM contre L858R/T790M, respectivement. AZD-9291 surmonte la résistance médiée par T790M aux inhibiteurs de l'EGFR dans le cancer du poumon.

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AZD-9291 Chemical Structure

Cas No.: 1421373-65-0

Taille Prix Stock Qté
10mM (in 1mL DMSO)
59,00 $US
En stock
5mg
44,00 $US
En stock
10mg
56,00 $US
En stock
50mg
153,00 $US
En stock
500mg
610,00 $US
En stock

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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment[1]:

Cell lines

Human lung cancer cells with EGFR-mutations or wild type EGFR stable expression

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Applications

AZD9291 potently inhibits EGFR phosphorylation in EGFRm+ (e.g. PC9; < 25 nM) and EGFR m+/T790M (e.g. H1975; < 25 nM) cell lines in vitro, whilst demonstrating much less activity against wild-type EGFR lines (e.g. LoVo; > 500 nM). Consistently, AZD9291 showed significantly more potent inhibition of proliferation in mutant EGFR cell lines compared to wild-type in vitro.

Animal experiment[1]:

Animal models

EGFRm+ and EGFRm+/T790M transgenic mice

Dosage form

5 mg/kg

Applications

AZD9291 administered once daily orally at 5 mg/kg caused profound regression of tumours across EGFRm+ (PC9; 178% growth inhibition) and EGFRm+/T790M (H1975; 119% growth inhibition) tumour models in vivo, after 14 days dosing. Furthermore 5 mg/kg AZD9291 was sufficient to cause significant shrinkage of EGFRm+ and EGFRm+/T790M transgenic mouse lung tumours. Tumour growth inhibition was associated with profound inhibition of EGFR phosphorylation and key downstream signaling pathways such as AKT and ERK. Chronic long-term treatment of PC9 and H1975 xenograft tumours with AZD9291 led to a complete and sustained macroscopic response, with no visible tumours after 40 days dosing, and being maintained beyond 100 days. Furthermore, pre-clinical data also indicates that AZD9291 could target tumours that have acquired resistance to the more recently identified HER2-amplification mechanism, thus potentially extending its benefit in TKI resistant patients.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

1. Darren Cross1, Sue Ashton1, Caroline Nebhan2 et al. AZD9291: an irreversible, potent and selective third generation tyrosine kinase inhibitor (TKI) targeting EGFR activating (EGFRm+) and resistance (T790M) mutations in advanced lung adenocarcinoma. Mol Cancer Ther 2013;12(11 Suppl):A109.

Background

AZD-9291 est un inhibiteur irréversible de la kinase EGFR mutante avec des valeurs IC50 de 15nM, 17nM et 480nM, respectivement pour L858R/T790M, ex19del et EGFR sauvage [1].

Une série de mutations provoque la résistance de l'EGFR, et l'AZD-9291 est développé comme un inhibiteur irréversible et sélectif du mutant EGFR. L'AZD-9291 se lie au site de liaison à l'ATP de l'EGFR en ciblant Cys 797. Dans le test d'enzyme recombinante EGFR, l'AZD-9291 montre une puissance environ 200 fois supérieure contre le mutant EGFR que contre le type sauvage. L'AZD-9291 n'exerce pas d'activité significative sur les autres kinases récepteurs. Les tests in vitro montrent que l’AZD-9291 peut inhiber la phosphorylation de l’EGFR avec une valeur IC50 plus faible dans les lignées cellulaires portant des mutants sensibilisants de l’EGFR que dans les lignées cellulaires sauvages. De plus, AZD9291 peut induire une réduction profonde du volume des tumeurs mutantes EGFR à faibles doses dans des modèles xénogreffes. Il en va de même pour les modèles tumoraux transgéniques chez la souris. Les souris traitées avec AZD9291 à la dose de 5 mg/kg/jour présentent une réduction de 80% du volume tumoral [1].

References:
[1] Darren A. E. Cross, Susan E Ashton, Serban Ghiorghiu, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discovery. 2014, June.

Chemical Properties

Cas No. 1421373-65-0 SDF
Synonymes osimertinib
Canonical SMILES CN1C=C(C2=NC(NC3=C(OC)C=C(N(CCN(C)C)C)C(NC(C=C)=O)=C3)=NC=C2)C4=C1C=CC=C4
Formula C28H33N7O2 M.Wt 499.61
Solubility ≥ 24.98mg/mL in DMSO Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 2.0016 mL 10.0078 mL 20.0156 mL
5 mM 0.4003 mL 2.0016 mL 4.0031 mL
10 mM 0.2002 mL 1.0008 mL 2.0016 mL
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Average Rating: 5 ★★★★★ (Based on Reviews and 14 reference(s) in Google Scholar.)

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